Two Distinct Sets of Ca 2+ and K + Channels Are Activated at Different Membrane Potentials by the Climbing Fiber Synaptic Potential in Purkinje Neuron Dendrites
| Autor: | Karima Ait Ouares, Luiza Filipis, Panayiota Poirazi, Marco Canepari, Alexandra Tzilivaki |
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| Přispěvatelé: | Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute of Molecular Biology and Biotechnology, Foundation for Research & Technolgy - Hellas |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
BK channel [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [SDV]Life Sciences [q-bio] Cerebellar Purkinje neuron Dendrite SK channel 03 medical and health sciences 0302 clinical medicine NEURON modelling calcium channels medicine Ion channel ComputingMilieux_MISCELLANEOUS Synaptic potential Membrane potential neuronal dendrites Voltage-dependent calcium channel biology Chemistry General Neuroscience Depolarization potassium channels 030104 developmental biology medicine.anatomical_structure biology.protein Biophysics 030217 neurology & neurosurgery climbing fibre |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2019, 39 (11), pp.1969-1981. ⟨10.1523/JNEUROSCI.2155-18.2018⟩ |
| ISSN: | 0270-6474 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.2155-18.2018⟩ |
| Popis: | In cerebellar Purkinje neuron dendrites, the transient depolarization associated with a climbing fiber (CF) EPSP activates voltage-gated Ca2+channels (VGCCs), voltage-gated K+channels (VGKCs), and Ca2+-activated SK and BK K+channels. The resulting membrane potential (Vm) and Ca2+transients play a fundamental role in dendritic integration and synaptic plasticity of parallel fiber inputs. Here we report a detailed investigation of the kinetics of dendritic Ca2+and K+channels activated by CF-EPSPs, based on optical measurements ofVmand Ca2+transients and on a single-compartment NEURON model reproducing experimental data. We first measuredVmand Ca2+transients associated with CF-EPSPs at different initialVm, and we analyzed the changes in the Ca2+transients produced by the block of each individual VGCCs, of A-type VGKCs and of SK and BK channels. Then, we constructed a model that includes six active ion channels to accurately match experimental signals and extract the physiological kinetics of each channel. We found that two different sets of channels are selectively activated. When the dendrite is hyperpolarized, CF-EPSPs mainly activate T-type VGCCs, SK channels, and A-type VGKCs that limit the transientVm∼ 2+spikes. Thus, the potentially activity-dependent regulation of A-type VGKCs, controlling the activation of this second set of channels, is likely to play a crucial role in signal integration and plasticity in Purkinje neuron dendrites.SIGNIFICANCE STATEMENTThe climbing fiber synaptic input transiently depolarizes the dendrite of cerebellar Purkinje neurons generating a signal that plays a fundamental role in dendritic integration. This signal is mediated by two types of Ca2+channels and four types of K+channels. Thus, understanding the kinetics of all of these channels is crucial for understanding PN function. To obtain this information, we used an innovative strategy that merges ultrafast optical membrane potential and Ca2+measurements, pharmacological analysis, and computational modeling. We found that, according to the initial membrane potential, the climbing fiber depolarizing transient activates two distinct sets of channels. Moreover, A-type K+channels limit the activation of P/Q-type Ca2+channels and associated K+channels, thus preventing the generation of Ca2+spikes. |
| Databáze: | OpenAIRE |
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